Postnatally induced metabolic and oxidative changes associated with maternal high-fat consumption were mildly affected by Quercetin-3-O-rutinoside treatment in rats.

Oxidative stress is usually associated with prolonged intake of high-fat diet (HFD). However, little is known about the impact of maternal HFD on endogenous modulation of antioxidant-defence-enzyme-network, its link to adverse fetal growth and overall effects of Quercetin-3-o-rutinoside (QR) supplementation. Sprague-Dawley rats were initially assigned to normal diet (ND) or HFD for 8 weeks and mated. Post-conception, rats were further divided into four groups, of which two groups had diets supplemented with QR while others continued with their respective diets until delivery. Measurements include food and water consumption, physical parameters (body weight, body mass index (BMI) and fur appearance), oral glucose tolerance, lipid profiles, and placental/liver oxidative changes. We observed that water consumption was significantly increased in dams fed HFD without marked differences in food intake, body weight, BMI and glucose tolerance. Surprisingly, offspring of HFD-fed dams had reduced body weight marked by delayed fur appearance compared to the ND offspring. In dams, there were alterations in lipid profile. Lipid peroxidation was increased in the placenta and liver of gestational day (GD) 19 HFD-fed dams and their postnatal day (PND) 21 male offspring. There was evidence of HFD-induced nitrosative stress in dams and PND28 female offspring. Adaptive defence indicate decreased placenta and liver superoxide dismutase (SOD) levels as well as differential changes in total antioxidant capacity (TAC) and catalase (CAT) activity in HFD treated dams and their progenies. Overall, the results indicate that intrauterine metabolic alterations associated with maternal high-fat consumption may induce oxidative challenge in the offspring accompanied by mild developmental consequences, while QR supplementation has little or no beneficial effects.

Cocaine-induced inheritable epigenetic marks may be altered by changing early postnatal fostering.

Here, we explored the hypothesis that parental cocaine exposure could alter epigenetic machinery in their drug-naive offspring while early postnatal fostering may further modify the accompanied neurochemical and functional components. Variant drug-naive pups were produced from cocaine-exposed or unexposed C57BL/6 female mice that were matched with their male counterparts for mating. Within 3 days of birth, half of the pups were cross-fostered and nurtured by non-biological lactating dams. The pups were initially examined for locomotor activity and memory performance and subsequently for changes in DNA methylation in promoter regions of cAMP response element modulator (Crem) and Fosb in the prefrontal cortex at 48 days postnatum. The impact of postnatal fostering on these parameters was also investigated. Our results showed that cocaine exposure significantly decreased both Crem and Fosb methylation in the prefrontal cortex of progenitor mice, while similar patterns of methylation were replicated in the brains of drug-naive non-fostered offspring mice but reversed by postnatal fostering. Furthermore, offspring raised by cocaine-exposed dams were impaired in discriminative learning and exhibited memory decline, whereas locomotor activity remains unaltered in all groups of mice. Our data provide some evidence that indirect exposure to cocaine may cause marked epigenetic changes within the cortical networks of drug-naive descendants and that mediation by Crem/Fosb signalling in this brain region may be beneficial, while early postnatal fostering may further engineer molecular switching that may predispose the individual to future risky behaviours as well as accumulative potential to developing cognitive impairment later in life.

Differential epigenetic changes in the hippocampus and prefrontal cortex of female mice that had free access to cocaine.

Alterations in gene expression within the neural networks of prefrontal cortex (PFC) and hippocampus (HPC) are known to contribute to behavioural phenotypes associated with drug intake. However, the functional consequences of regulated expression patterns of Fosb and Crem (cAMP response element modulator) in both brain regions in response to volitional intake of cocaine in social environment is yet to be explored. Here, we first exposed young adult mice to cocaine (300 mg/L) and water concurrently for 30 days in the IntelliCage to investigate consumption preference, and subsequently for 28 days during which persistent motivated drug seeking behaviours were examined. Thereafter, locomotor activity and memory performance of the mice were assessed. DNA methylation status in the promoters of Fosb and Crem genes were also evaluated. We show that mice that had extended access to cocaine exhibited motivational deficit and demonstrated decreased locomotor activity and intact recognition memory. These changes were accompanied by hypomethylation or hypermethylation in the promoters of Fosb and Crem genes in the PFC and HPC of the cocaine-experienced mice, respectively. Together, these findings correlate the molecular changes to behavioural effects of the treatment and further suggests a possible activation of prefrontal cortical networks by social interaction episodes in the IntelliCage which possibly enhanced behavioural control that dampens mice sensitivity to cocaine rewards. Furthermore, our data delineate the molecular response of Crem and Fosb to oral cocaine in group-housed mice and demonstrates differential regulation of activities within the substrate brain regions studied.

Epigenetics: a link between addiction and social environment.

The detrimental effects of drug abuse are apparently not limited to individuals but may also impact the vulnerability of their progenies to develop addictive behaviours. Epigenetic signatures, early life experience and environmental factors, converge to influence gene expression patterns in addiction phenotypes and consequently may serve as mediators of behavioural trait transmission between generations. The majority of studies investigating the role of epigenetics in addiction do not consider the influence of social interactions. This shortcoming in current experimental approaches necessitates developing social models that reflect the addictive behaviour in a free-living social environment. Furthermore, this review also reports on the advancement of interventions for drug addiction and takes into account the emerging roles of histone deacetylase (HDAC) inhibitors in the etiology of drug addiction and that HDAC may be a potential therapeutic target at nucleosomal level to improve treatment outcomes.